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*Biomarkers of acute respiratory allergen exposure: Screening for sensitization potential
Citation:
PUCHEU-HASTON, C. M., L. B. COPELAND, E. BOYKIN, M. D. WARD, AND B. VALLANAT. *Biomarkers of acute respiratory allergen exposure: Screening for sensitization potential. TOXICOLOGY AND APPLIED PHARMACOLOGY. Academic Press Incorporated, Orlando, FL, 244(2):144-155, (2010).
Impact/Purpose:
This study demonstrates that a single respiratory exposure of naive mice to a sensitizing extract induces an inflammatory response which is distinct in phenotype and gene expression from the response to control protein. From these data, we have compiled a list of candidate biomarkers ofexposure to respiratory sensitizing agents. These biomarkers rna facilitate im rovements in hazard screenin methods
Description:
Effective hazard screening will require the development of high-throughput or in vitro assays for the identification of potential sensitizers. The goal of this preliminary study was to identify potential biomarkers that differentiate the response to allergens vs non-allergens following an acute exposure in natve individuals. Female BALB/c mice received a single intratracheal aspiration exposure to Metarhizium anisopliae crude antigen (MACA) or bovine serum albumin (BSA) in Hank's Balanced Salt Solution (HBSS) or HBSS alone, Mice were sacrificed after 1, 3, 6, 12, 18 and 24h. Bronchoalveolar lavage fluid (BALF) was evaluated to determine total and differential cellularity, total protein concentration and LDH activity, RNA was isolated from lung tissue for microarray analysis and qRT-PCR. MACA administration induced a rapid increase in BALF neutrophils, lymphocytes, eosinophils and total protein compared to BSA or HBSS. Microarray analysis demonstrated differential expression of genes involved in cytokine production, signaling, inflammatory cell recruitment, adhesion and activation in 3h and 12h MACA-treated samples compared to BSA or HBSS. Further analyses allowed identification of -100 candidate biomarker genes. Eleven genes were selected for further assessment by qRT-PCR. Of these, 6 demonstrated persistently increased expression (CcI1l, Cc122, Ccll, Cxcl1 0, Cxcl2, Saa1), while C3ar1 increased from 6-24h. In conclusion, a single respiratory exposure of mice to an allergenic mold extract induces an inflammatory response which is distinct in phenotype and gene transcription from the response to a control protein. Further validation of these biomarkers with additional allergens and irritants is needed. These biomarkers may facilitate improvements in screening methods.
